Advancements Emerging in Nonmetastatic and mCRPC Paradigms

Caroline Seymour

Published: Friday, Jan 25, 2019

Tanya Dorff, MD

Two critical clinical trials—SPARTAN and PROSPER—served as the basis for the 2018 FDA approvals of apalutamide (Erleada) and enzalutamide (Xtandi), respectively, agents that have drastically changed the standard of care for patients with nonmetastatic castration-resistant prostate cancer (CRPC), said Tanya B. Dorff, MD.

During the 2018 OncLive® State of the Science SummitTM on Genitourinary Cancers, Dorff explained that these approvals have established a foundation for subsequent progress for patients with nonmetastatic CRPC.

In the metastatic castration-resistant prostate cancer (mCRPC) space, more research is moving forward with immunotherapy, PARP inhibitors, and imaging techniques.

“As we define molecular subsets, and we find the drugs that have a big impact, such as PARP inhibitors in patients with DNA repair deficiency, it will likely be amplified in earlier [lines of therapy]. It’s what we’ve seen with docetaxel in CHAARTED and abiraterone acetate (Zytiga) and docetaxel in STAMPEDE and LATITUDE,” said Dorff. “The earlier we use these drugs, the better. The big space to focus on is trying to bring more durable responses to patients, provided we don't do it at the cost of quality of life (QoL).”

In an interview with OncLive®during the meeting, Dorff, associate clinical professor in the Department of Medical Oncology and Therapeutics Research, and head of the genitourinary cancers program at City of Hope, discussed landmark approvals in nonmetastatic CRPC and anticipated developments in metastatic CRPC.

OncLive®: What trials have defined the field of nonmetastatic CRPC?

Dorff: For nonmetastatic CRPC, there were 2 landmark studies that have now changed the way we practice. First and foremost, it's important to image patients whose prostate-specific antigen (PSA) is rising despite castration therapy, so that we can correctly categorize them as metastatic or nonmetastatic––even oligometastatic versus large-volume metastatic disease. When we do find patients who are truly nonmetastatic castration-resistant, but we can't find anything on conventional imaging, we need to check their doubling time to categorize them as high-risk or not. We use a PSA doubling time cutoff of £10 months. That's what was used in both of the trials.

If a patient meets all those criteria, we now have treatment options for them, whereas before we really didn't. We used to do some secondary hormonal manipulations, but there was nothing we knew would improve survival. Both apalutamide and enzalutamide were studied in large randomized trials and showed a positive primary endpoint of metastasis-free survival (MFS). This is a new endpoint for the prostate cancer community, but it led to the FDA approval of these drugs in this context. It’s clinically meaningful and resonates with patients.

We don’t have comparative data between apalutamide and enzalutamide. Either one is a perfectly acceptable option. There are some slight differences between their side effect profiles, but generally speaking there is no major reason to choose one or the other.

Additionally, QoL seems to be maintained on these drugs. The other major thing to emphasize is that fractures were seen on one of the studies. These men have been castrated for quite a while and are going to continue on castration therapy, so we have to pay attention to bone supportive therapy when we're treating men in this earlier-disease setting.

Do payers have a preference with regard to apalutamide and enzalutamide?

It's possible that insurers may have a preference. I did have that situation with one patient. [A payer may opt for one drug] if it is priced more favorably for their group. Falls or seizures are side effects we traditionally associate with enzalutamide. If a patient has had issues with falls or seizures, one might think we should choose apalutamide.